Published Online
on July 15, 2002

A more recent version of this article appeared on July 30, 2002

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Submitted on January 14, 2002
Revised on May 6, 2002
Accepted on May 6, 2002

Potentiated Sympathetic Nervous and Renin-Angiotensin Systems Reduce Nonlinear Correlation Between Sympathetic Activity and Blood Pressure in Conscious Spontaneously Hypertensive Rats

Katsufumi Sakata MD, Hiroo Kumagai MD^*, Motohisa Osaka MD, Toshiko Onami MD, Tomokazu Matsuura MD, Masaki Imai MD, and Takao Saruta MD

From the Department of Internal Medicine, Keio University School of Medicine, Tokyo (K.S., H.K., T.O., T.M., M.I., T.S.), and the Institute of Gerontology, Nippon Medical School, Kawasaki (M.O.), Japan.

^* To whom correspondence should be addressed. E-mail: hkumagai{at}sc.itc.keio.ac.jp.

Background—Patients with a reduced nonlinear component of heart rate regulation have a poorer outcome.

Methods and Results—We investigated whether a nonlinear correlation between renal sympathetic nerve activity (RSNA) and blood pressure or renal blood flow is reduced in conscious, spontaneously hypertensive rats (SHR) by comparing them with normotensive Wistar-Kyoto rats (WKY). We also determined the linearity and nonlinearity of the correlation in SHR who were given an angiotensin II receptor blocker, candesartan, orally for 2 weeks. The RSNA value was higher in SHR than in WKY, and coherence peaks of transfer function were found at 0.05 and 0.80 Hz (ie, below respiratory- and cardiac-related fluctuations). The coherence (linearity) of the transfer function was significantly higher and gain was smaller in SHR than in WKY. Because mutual information values (linear and nonlinear correlation) were similar in both strains, we found the nonlinear correlation to be lower in SHR than in WKY. Time delay values calculated by the mutual information method demonstrated that RSNA preceded blood pressure and renal blood flow by 0.5 to 1.0 s. In SHR given candesartan, the RSNA value was lower, and the linearity was lower and nonlinearity higher than SHR given vehicle.

Conclusions—Linear correlation between RSNA and blood pressure or renal blood flow was higher in SHR than in WKY, whereas the nonlinear correlation was lower. Oral treatment with candesartan increased the nonlinearity and reduced the linearity in SHR. Increased RSNA and the renin-angiotensin system may be responsible for the lower nonlinearity and higher linearity in hypertension.

Key words: hypertension • nervous system, sympathetic • angiotensin

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